title: Overexpression of Bmi-1 contributes to the invasion and metastasis of hepatocellular carcinoma by increasing the expression of matrix metalloproteinase (MMP)‑2, MMP-9 and vascular endothelial growth factor via the PTEN/PI3K/Akt pathway.
abstract: Hepatocellular carcinoma (HCC) is one of the most common malignant tumours and it carries a poor prognosis due to a high rate of recurrence or metastasis after surgery. Bmi-1 plays a significant role in the growth and metastasis of many solid tumours. However, the exact mechanisms underlying Bmi-1-mediated cell invasion and metastasis, especially in HCC, are not yet known. In the present study, we sought to evaluate the expression of Bmi-1 in HCC samples and its relationship with clinicopathological characteristics and prognostic value, we also investigated related mechanisms underlying Bmi-1-mediated cell invasion in HCC. Our results showed that Bmi-1 is upregulated in HCC tissues compared to matched non-cancer liver tissues; and its expression is positively associated with tumour size, metastasis, venous invasion and AJCC TNM stage, respectively; multivariate analysis showed that high expression of Bmi-1 was an independent prognostic factor for overall survival. In addition, the shRNA-mediated inhibition of Bmi-1 reduced the invasiveness of two HCC cell lines in vitro by upregulating phosphatase and the tensin homolog deleted on chromosome 10 (PTEN) expression, inhibiting the phosphatidylinositol 3-kinase (PI3K)/Akt signalling pathway and downregulating the expression and activities of matrix metalloproteinase (MMP)-2 and MMP-9 and vascular endothelial growth factor (VEGF). These data demonstrate that Bmi-1 plays a vital role in HCC invasion and that Bmi-1 is a potential therapeutic target for HCC.
authors.affiliation: Department of Hepatobiliary Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shannxi 710032, P.R. China.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Li
authors.forename: Zhaoxu
authors.initials: Z
authors.lastname: Yang
authors.forename: Wenjie
authors.initials: W
authors.lastname: Song
authors.forename: Liang
authors.initials: L
authors.lastname: Zhou
authors.forename: Qingjun
authors.initials: Q
authors.lastname: Li
authors.forename: Kaishan
authors.initials: K
authors.lastname: Tao
authors.forename: Jingshi
authors.initials: J
authors.lastname: Zhou
authors.forename: Xing
authors.initials: X
authors.lastname: Wang
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Zheng
authors.forename: Nan
authors.initials: N
authors.lastname: You
authors.forename: Kefeng
authors.initials: K
authors.lastname: Dou
authors.forename: Haimin
authors.initials: H
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular; D053492:Elafin / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis* / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D048054:Mitogen-Activated Protein Kinase 7 / Q000096:biosynthesis* / Q000235:genetics; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology; D009367:Neoplasm Staging; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D053492:Elafin; C506806:PI3 protein, human; D042461:Vascular Endothelial Growth Factor A; D051057:Proto-Oncogene Proteins c-akt; C481581:MAPK7 protein, human; D048054:Mitogen-Activated Protein Kinase 7; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9